EPIVIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EPIVIR (EPIVIR).
Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI). It is phosphorylated intracellularly to lamivudine triphosphate, which competes with endogenous deoxycytidine triphosphate for incorporation into viral DNA by HIV reverse transcriptase and hepatitis B virus polymerase, resulting in DNA chain termination.
| Metabolism | Lamivudine undergoes limited hepatic metabolism (approximately 5-10%) to a trans-sulfoxide metabolite. It is predominantly eliminated unchanged in the urine via active renal secretion. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 70% of elimination, with active tubular secretion contributing significantly. Biliary/fecal elimination is minimal (<10%). |
| Half-life | Terminal elimination half-life is 5 to 7 hours in adults with normal renal function. In neonates, half-life is prolonged (up to 12-18 hours). Clinically, dosing interval adjustments are required for creatinine clearance <30 mL/min. |
| Protein binding | Limited protein binding (<36%). Binding occurs primarily to albumin, but is not clinically significant for drug interactions. |
| Volume of Distribution | Volume of distribution is approximately 1.3 L/kg, indicating distribution into total body water and penetration into tissues including the central nervous system. |
| Bioavailability | Oral bioavailability is 86% (range 80-90%) in adults, and approximately 68% in neonates. No other routes of administration are approved. |
| Onset of Action | Oral: Antiretroviral effect begins within hours, with maximum suppression of HIV RNA achieved in 4-6 weeks. No parenteral formulation available. |
| Duration of Action | Duration of antiviral effect is 12 hours based on dosing interval (every 12 hours). Continuous suppression requires consistent dosing; missed doses may lead to viral rebound. |
| Molecular Weight | 229.26 |
300 mg orally once daily or 150 mg orally twice daily
| Dosage form | TABLET |
| Renal impairment | CrCl >=50 mL/min: 300 mg daily or 150 mg twice daily; CrCl 30-49: 150 mg once daily; CrCl 15-29: 150 mg first dose then 100 mg once daily; CrCl 5-14: 150 mg first dose then 50 mg once daily; CrCl <5: 50 mg first dose then 25 mg once daily |
| Liver impairment | No dose adjustment required for Child-Pugh A or B; Child-Pugh C: no data, use with caution |
| Pediatric use | 3 months to 16 years: 4 mg/kg orally twice daily (max 150 mg per dose); do not use Epivir single-dose tablets in children <14 kg |
| Geriatric use | No specific adjustment based on age alone; monitor renal function and adjust dose accordingly per renal guidelines |
| 1st trimester | Use only if benefit outweighs risk; teratogenic risk low but limited data in first trimester. |
| 2nd trimester | Safe with caution; monitor maternal liver function and HIV viral load. |
| 3rd trimester | Safe with caution; monitor for neonatal anemia and pancreatitis. |
Clinical note
Comprehensive clinical and safety monograph for EPIVIR (EPIVIR).
| Placental transfer | Extensive placental transfer; cord blood levels similar to maternal plasma. |
| Breastfeeding | Lamivudine is excreted into breast milk at low levels; considered compatible with breastfeeding. Monitor infant for adverse effects (e.g., anemia, pancreatitis). |
| Lactation Rating |
â– FDA Black Box Warning
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination, including lamivudine. Discontinue lamivudine if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.
| Serious Effects |
Hypersensitivity to lamivudine or any component
| Precautions | Lactic acidosis and severe hepatomegaly with steatosis, Exacerbation of hepatitis B after discontinuation (severe acute exacerbations may occur), Pancreatitis (especially in pediatric patients with advanced HIV disease), Hepatic decompensation in patients co-infected with HIV and hepatitis C virus receiving interferon with or without ribavirin, Immune reconstitution syndrome, Risk of emergence of resistant HIV variants if used alone |
| Food/Dietary | Take with or without food. No significant food interactions. |
Loading safety data…
| L2 (Probably Compatible) |
| Teratogenic Risk | Lamivudine (EPIVIR) is classified as FDA Pregnancy Category C. In first trimester, the Antiretroviral Pregnancy Registry reports no increased risk of major birth defects compared to background rate (prevalence 2.9 per 100 live births). Data from the Registry show no significant association with congenital anomalies for lamivudine-containing regimens. Second and third trimester use is not associated with fetal toxicity; however, there is a theoretical risk of mitochondrial toxicity with NRTIs. Placental transfer is high, achieving fetal concentrations similar to maternal. |
| Fetal Monitoring | Monitor maternal liver function tests, renal function, complete blood count, and HIV viral load. Observe for signs of lactic acidosis and hepatic steatosis, particularly in pregnant women. Monitor infant for possible mitochondrial toxicity (rare) and check infant HIV status if maternal HIV positive. Recommend echocardiography if fetal arrhythmia suspected (rare). |
| Fertility Effects | No adverse effects on fertility in males or females have been demonstrated in animal studies. In humans, no significant impact on fertility outcomes reported. Lamivudine is commonly used in HIV-positive individuals, and effective viral suppression improves overall reproductive health. |
| Clinical Pearls | Monitor renal function; adjust dose for CrCl <50 mL/min. Avoid use in HBV/HIV coinfection without antiretroviral therapy due to risk of HBV resistance. Lactic acidosis and severe hepatomegaly with steatosis reported. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop without consulting your doctor. · Report any signs of lactic acidosis (e.g., unexplained fatigue, muscle pain, difficulty breathing) or liver problems (e.g., jaundice, dark urine). · If you have hepatitis B, stopping lamivudine may cause severe liver flare-ups. · This medication does not cure HIV or prevent transmission; practice safe sex and avoid sharing needles. |